CYP2C9 is a major member of cytochrome P450 superfamily of enzymes, which hydroxylates about 16% of drugs that are in current clinical use and contributes to the metabolism of a number of clinically important substrate drugs such as warfarin, phenytoin, and oral hypoglycemic. The CYP2C9 gene encodes a protein of 490 amino acids localized to the endoplasmic reticulum. This protein is a that play a major role in the metabolism of several drugs. The effect of CYP2C9 inhibitors or inducers with warfarin can be compensated for with dosage adjustments of the CYP2C9 substrate. Lower warfarin doses are needed to achieve anticoagulation in patients with *2 or *3 variants, because it will be metabolized less efficiently and will remain in circulation longer. Drugs that inhibit CYP2C9 activity, in some cases, increase some medications in the plasma, leading to toxicity and adverse reactions.
The CYP2C9 gene is mapped to chromosome 10q23.33. The gene consists of nine coding exons and is about 51 kb in length. The CYP2C9 SNPs are: *1 (wild-type), which metabolizes warfarin normally, the two polymorphic versions, *2 (430C>T) that reduces warfarin metabolism by 30%, and *3 (1075A>C) that reduces warfarin metabolism by 90%. The prevalence of these variants varies by race; 10% of the Caucasians have the *2 variant, while 6% have the *3. In African or Asian descent, variants *2 and *3 are rare (< 2%).
Pathare et al. (2012) carried out a study of genetic polymorphisms of the CYP2C9, CYP4F2, and VKORC1 loci together for 240 (180 males and 60 females) healthy Omani participants. Using direct sequencing for exons 3 and 7 of CYP2C gene for 220 samples, the frequency for combined CYP2C9 mutant allele (CYP2C9 *2, *3 and *8) in Omanis was 0.16; the homozygous and compound heterozygous state was about 4% among Omanis, while the heterozygous state was 24%. The frequency of warfarin-sensitive homozygous and compound heterozygous was of intermediate value between Caucasians and African Americans/Asians. While CYP2C9 (*4, *5 and *9) alleles were not found in Omani participants. Two of the patients were found to have warfarin-sensitive genotype for both CYP2C9 and VKORC1 loci together (1.2%).
Tanira et al. (2007) correlated CYP2C9 genotypes with warfarin dosage in 189 Omani patients on Warfarin. Of these, 13% and 6% patients were heterozygous for the CYP2C9*2 and CYP2C9*3 alleles, respectively, while 1% were homozygous for the CYP2C9*2 allele. This was the first time CYP2C9*2 homozygosity was reported in an Asian or African population. The frequency of CYP2C9*2 and CYP2C9*3 alleles were calculated at 0.079 and 0.029, respectively. The mean maintenance dose of warfarin for those with wildtype alleles was found to be higher than the mean maintenance dose in patients with variant alleles.
Mirghani et al. (2011) studied a cohort of 192 healthy unrelated Saudi subjects (82 men and 110 women) to investigate the frequencies of the major variants of the CYP2C9 in Saudi Arabians. The subjects were assumed healthy by their medical history. The average age of the subjects was around 32-years. The determinations of *2 and *3 cover more than 98% of several populations. For this reason, only these two major variants of CYP2C9 in the Saudi population were analyzed. The most common genotype was *1*1 with a frequency of 64.1% (n = 123). The rare homozygous mutated genotypes were between 1.6% and 2.1%. The frequencies of heterozygous subjects were 17.2% and 13.0% for the *2 and *3 variants, respectively. Accumulating data demonstrate the decreased catalytic activity of the enzyme encoded by *2 or *3 for different drug substrates of CYP2C9. The authors concluded that in Saudi Arabians, the frequencies of the major CYP2C9 variants, *2 and *3, are similar to those of Caucasians and significantly higher than those of Orientals and Africans.
Shrif et al. (2011) studied the possible association between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in 203 Sudanese warfarin-treated patients. Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8 mg/day, P?